In this research proposal entitled "Structural Analysis of Type II collagen Under Mechanical Stress Using Atomic Force Microscopy," the mechanochemical property of type II collagen, especially sensitivity of specific cleavages by collagenases under mechanical stress, will be investigated. Type II collagen is a major constituent of articular cartilage and the most common joint disease, osteoarthritis, is characterized, in part, by the progressive loss of articular cartilage. A question addressed in this proposal is whether the metabolic turn-over rates of type II collagen is stimulated by mechanical stress. A specific hypothesis to be tested is: Type II collagen behaves like a stiff linear spring under mechanical stress, and the mechanically stressed type ii collagen is degraded at a higher turn-over rate by matrix metalloproteinase such as collagenase 1, 2, or 3 than the unstressed counterpart. The above hypothesis will be tested by visualizing individual type II collagen molecules by atomic force microscopy. Collagen molecules will be stretched and immobilized on a flat surface. Immunobilized molecules will be incubated with various collagenases and the site of specific cleavages will be determined individually along stretched molecules. The proposed research on type II collagen under mechanical stress will contribute to elucidate the role of mechanical stress in osteoarthritis and shed the light on the complex interplay of metabolic and biomechanical factors in the loss of articular cartilage.